PDGF Gene Therapy Promotes Periodontal Bone and Cemental Repair

Introduction: Platelet-derived growth factor (PDGF) has potent effects on the regeneration of soft and hard tissues. PDGF stimulates partial repair of periodontal osseous lesions as evidenced by results from preclinical and clinical trials. Limitations of protein delivery to periodontal defects include transient biological activity of PDGFs and bioavailability of factors at the wound site. Objective: The objective of this investigation was to determine the ability of in vivo PDGF-B gene transfer to stimulate periodontal regeneration in large surgically-created periodontal alveolar bone wounds. Methods: Osseous defects were treated with a 2.6% collagen carrier or carrier containing recombinant adenoviruses encoding a control virus luciferase (Ad-luc; 5 x 10⁹ particles (PN)/wound), or PDGF-B (Ad-PDGF-B at two dose levels (5 x 10⁸ (low dose)/wound or 5 x 10⁹ PN (high dose)/wound). Parameters of periodontal wound repair were measured and included bone length, bone area and length of new cementum using image analysis. The collagen carrier with or without genes was delivered to the buccal aspect of the mandibular first and second molars (defect size: 3 x 2 x 2 mm; n=3-6 animals/group) in Sprague-Dawley rats. Block biopsies were harvested at 3, 7, 14, and 28 days post-gene delivery and descriptive histology and histomorphometric analyses were performed. Results: Results revealed defects treated with high dose Ad-PDGF-B demonstrated strong evidence of bone and cementum regeneration. Computer-assisted image analysis showed a nearly 7-fold increase in bone density and 6-fold increase in cemental repair in high dose Ad-PDGF-B treated sites, while lesions treated with the low dose Ad-PDGF, Ad-luc or collagen alone that showed limited hard tissue formation. Conclusion: We conclude direct gene transfer of PDGF-B stimulates alveolar bone and cementum regeneration in large periodontal defects. Gene therapy utilizing PDGF-B may offer potential for periodontal engineering applications. (Funded by NIH/NIDCR DE 11960 and DE 13397)